Dataset Information

HLA-B?44 Is Associated with Dengue Severity Caused by DENV-3 in a Brazilian Population.

ABSTRACT: Human leukocyte antigen (HLA) alleles have been correlated with susceptibility or resistance to severe dengue; however, few immunogenetic studies have been performed in Latin American (LA) populations. We have conducted immunogenetic studies of HLA class I and II alleles in a cohort of 187 patients with DENV-3 infection and confirmed clinical diagnosis of either severe dengue, known as dengue hemorrhagic fever (DHF), or the less severe form, dengue fever (DF), in Recife, Pernambuco, Brazil. An association analysis was performed using Fisher's association test, with odds ratios (ORs) calculated using conditional maximum likelihood estimates. HLA-B?44 (P = 0.047, OR = 2.025, 95% CI = 0.97-4.24) was found to be associated with increased susceptibility to DHF in response to DENV-3 infection. In addition, HLA-B?07 (P = 0.048, OR = 0.501, one-sided 95% CI = 0-0.99) and HLA-DR?13 (P = 0.028, OR = 0.511, one-sided 95% CI = 0-0.91) were found to be associated with resistance to secondary dengue infection by DENV-3. These results suggest that HLA-B?44 supertype alleles and their respective T-cell responses might be involved in susceptibility to severe dengue infections, whereas the HLA-B?07 supertype alleles and DR?13 might be involved in cross-dengue serotype immunity.

SUBMITTER: Xavier Eurico de Alencar L

PROVIDER: S-EPMC3684019 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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HLA-B∗44 Is Associated with Dengue Severity Caused by DENV-3 in a Brazilian Population.

Xavier Eurico de Alencar Liciana L de Mendonça Braga-Neto Ulisses U José Moura do Nascimento Eduardo E Tenório Cordeiro Marli M Maria Silva Ana A Alexandre Antunes de Brito Carlos C da Silva Maria da Paz Carvalho Mda P Gil Laura Helena Vega Gonzales LH Montenegro Silvia Maria Lucena SM Marques Ernesto Torres de Azevedo ET

Journal of tropical medicine 20130602

Human leukocyte antigen (HLA) alleles have been correlated with susceptibility or resistance to severe dengue; however, few immunogenetic studies have been performed in Latin American (LA) populations. We have conducted immunogenetic studies of HLA class I and II alleles in a cohort of 187 patients with DENV-3 infection and confirmed clinical diagnosis of either severe dengue, known as dengue hemorrhagic fever (DHF), or the less severe form, dengue fever (DF), in Recife, Pernambuco, Brazil. An a ...[more]

PMID: 23818909

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Project description:Around ten million people are infected with HTLV-1 worldwide, and 1-4% develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), characterized by an important degeneration of the spinal cord, which can lead to death. Distinct HLA alleles have been associated with either HAM/TSP susceptibility or protection. However, these HLA alleles set may change according to the population studied. Brazil is the second country in the number of HTLV-1-infected people and there are few reports addressing the HLA influence on HTLV-1 infection as well as on disease outcome. The objective of this study was to evaluate the influence of HLA alleles as a risk factor for HAM/TSP and the proviral load (PVL) levels, clinical progression, and death outcomes in an admixed Brazilian population. The HLA-A, -B, -C, and -DRB1 were genotyped in 375 unrelated HTLV-1-infected individuals divided into asymptomatic carriers (AC) (n = 165) and HAM/TSP (n = 210) in a longitudinal cohort from 8 to 22 years of follow-up. Because locus B deviated from Hardy-Weinberg Equilibrium for the study groups, the results represented for HLA-B alleles were inconclusive. The alleles HLA-A*68 and -C*07 were related to HAM/TSP risk in multivariate analysis. The alleles HLA-A*33, and -A*36 were associated with protection against disease progression in HAM/TSP patients, while -C*12, -C*14, and -DRB1*08 were associated with increased risk of death. In the AC group, the presence of, -C*06 and -DRB1*15 alleles influenced an increased PVL, in an adjusted linear regression model, while -A*30, -A*34, -C*06, -C*17 and -DRB1*09 alleles were associated with increased PVL in HAM/TSP group compared to HAM/TSP individuals not carrying these alleles. All these alleles were also related to increased PVL associated with clinical progression outcome. Increased PVL associated with the death outcome was linked to the presence of HLA-A*30. PVL has been associated with HLA, and several alleles were related in AC and HAM/TSP patients with or without interacting with clinical progression outcomes. Understanding the prognostic value of HLA in HAM/TSP pathogenesis can provide important biomarkers tools to improve clinical management and contribute to the discovery of new therapeutic interventions.

Dataset Information

HLA-B?44 Is Associated with Dengue Severity Caused by DENV-3 in a Brazilian Population.

Publications

HLA-B∗44 Is Associated with Dengue Severity Caused by DENV-3 in a Brazilian Population.

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